Project Summary (Abstract): Since its establishment in 2000, the Ohio Valley Node (OVN) has been one of the most productive of NIDA's Clinical Trials Network (CTN) nodes, both in leading and participating in multi-site trials. The OVN includes successful partnerships with four healthcare systems, two pharmacy networks, and six addiction specialty/ infectious disease programs. These collaborating sites span a seven-state region including some of the states most heavily impacted by opioid (Ohio, Kentucky, and West Virginia) and methamphetamine (Missouri, Kentucky, and North Dakota) use. The OVN includes Midwestern, Appalachian, Upper South, and Native American representation, which significantly enhances the geographical and cultural diversity of the CTN. The OVN Research Core is the driving force of the OVN and is led by Dr. Winhusen, one of the foremost experts in conducting multi-site addiction clinical trials in clinical practice settings. The OVN investigators have extensive expertise in substance use disorders (Winhusen, Brown, Burlew, Lyons, Montgomery, Lofwall, Walsh) and bioinformatics (Kaelber, Xu). The six members of the OVN research-implementation team bring > 60 years of combined experience conducting CTN clinical trials. If funded, our overall goal would be to utilize the wealth of experience and expertise gained over the past 19 years to conduct the research needed to address public health care crises, including the opioid use epidemic and the alarming increase in stimulant use. To this end, we would work with our healthcare partners to engage a diverse set of patients and service systems in areas highly impacted by substance use in CTN research. We would also contribute our expertise in conducting efficacy, effectiveness, and implementation trials testing the full range of interventions, from medications to behavioral interventions and health service innovations, for both opioid and stimulant use disorders. Moreover, we would contribute our expertise in the use of electronic health records for prospective and retrospective research studies, including the application of artificial intelligence to large healthcare datasets. In sum, we seek to continue providing scientific leadership, particularly on studies that could meaningfully impact clinical practice, and to effectively collaborate with a variety of professionals including treatment providers, investigators from diverse institutions, and staff of the Center for CTN (CCTN), clinical coordinating center (CCC) and data and statistics center (DSC) in support of the CTN mission.